Risk factors analysis for the progression to castration-resistant prostate cancer / 中华泌尿外科杂志

Objective To explore risk factors of the progression to castration-resistant prostate cancer(CRPC)after hormone therapy (HT).Methods A total of 178 patients with prostate cancer from February 2009 to February 2018 were enrolled to analyze the risk factors of the progression to castrationresistant prostate cancer after androgen deprivation therapy in Fujian Medical University Union Hospital.The mean age was72 years (range,49-91 years);the middle Gleason score was 7 (range,4-10);the middle PSA at the initiation of HT was 24.45 ng/ml (range,0.16-100.0 ng/ml);the middle time to PSA nadir was 9 months (range,0.5-69.0 months);the middle PSA nadir after HT was 0.030 ng/ml (range,0.003-78.670 ng/ml);the mean hemoglobin level was 131 g/L (range,64-184 g/L);the mean alkaline phosphatase level was 98 U/L (range,35-734 U/L);39 patients were diabetes mellitus (21.9％);82 patients were bone metastasis/visceral metastasis (46.1％);85 patients (47.8 ％) were in clinical T1 + T2;93 patients(52.2％)were in clinical T3 + T4.We studied the relationship between CRPC and these risk factors including age,Gleason score,PSA at the initiation of HT,PSA nadir after HT,the time to PSA nadir,hemoglobin level,alkaline phosphatase,bone metastasis/visceral metastasis,clinical T stage,diabetes mellitus by x2 test,univariate and multivariate Cox regression analysis methods.Results The middle follow-up time was 30 months (range,6-92 months).There were 74 of 178 patients progressed to CRPC after HT.The median time of progression to CRPC in this cohort was 15 months (range,4-47 months).On x2 test analysis,there were statistically significant differences between the progression to CRPC group after HT and the rest group in Gleason score (P ＜0.001),PSA nadir after HT (P ＜0.001),PSA at the initiation of HT (P =0.042),alkaline phosphatase (P =0.002),bone metastasis/visceral metastasis (P＜0.001) and clinical T stage (P ＜0.001).Additionally,on multivariate Cox regression analysis,Gleason score (OR =6.152,P ＜ 0.001),PSA nadir after HT (OR =3.022,P ＜ 0.004) and the time to PSA nadir (OR =0.375,P ＜0.001) were found to be significantly associated with the rapid progression to CRPC.Conelusions Gleason score,PSA nadir after HT and the time to PSA nadir were significantly associated with the progression to CRPC.Patients with higher PSA nadir or the shorter time to PSA nadir were more likely to progress to CRPC.

Assessment of risk factors for prostatic tumor invasion in patients undergoing radical cystectomy / 中华泌尿外科杂志

Objective To identify the risk factors for prostate-sparing cystectomy by evaluating the risk of prostatic invasion or incidental prostatic adenocarcinoma (PCa) in bladder cancer (BCa) patients undergoing radical cystectomy.Methods The patients undergoing radical cystectomy from 2009 to 2014 in Fujian Medical University Union Hospital were enrolled to analyze the risk factors of prostatic tumor invasion.These factors included age,tumor size,location,quantity,histologic grade and pathologic stage.Results In the 123 male patients,the mean age was 60 years (range,31-78 years);23 (18.7％) patients had BCa or PCa in the prostate;14 (11.4％) had prostatic Bca;11 (8.9％) had PCa.The risk factors of prostatic BCa included multifocal bladder tumors (OR =26.70,P =0.032),tumor in the bladder neck and trigone(OR =17.13,P =0.013),pathological stage (OR =26.70,P ＜ 0.001).Among the 11 patients with PCa,3(27.3％) patients had Gleason score of ≥7,8(72.7％) patients ≤6 and 2(18.2％) patients had extracapsular extension.Three patients had clinically significant PCa.The factor of advanced age was associated with incidental PCa (P =0.003).Conclusion The risk factors of prostatic tumor invasion in patients undergoing radical cystectomy included advanced age,bladder tumor in bladder neck and trigone,muhifocal bladder tumors,and advanced pathological stage.

The value of prostate-specific antigen density in the prediction of extraprostatic extension in patients with clinically organ-confined prostate cancer / 中华泌尿外科杂志

Objective To evaluate the role of PSA density with prostate volume determined by MR images in the prediction of extraprostatic extension in patients with clinically organ-confined prostate cancer.Method A total of 71 patients with clinically organ-confined prostate cancer who underwent radical prostatectomy from January 2009 to December 2013 were included in the study.MRI PSAD,preoperative total serum PSA (tPSA),free PSA/total PSA (fPSA/tPSA),biopsy Gleason score,prostate volume,age,body mass index in patients with extraprostatic extension were compared with those in patients with organ-confined disease.The receiver operating characteristic (ROC) curve was used to analyze the performance of each of the above parameters to predict the extraprostatic extension.Multivariate logistic regression analysis was used to select the independent influencing factors for extraprostatic extension.Results Pathologic examination revealed 32 patients were positive for extraprostatic extension and 39 paticnts had organ-confined disease.MRI PSAD(P ＜ 0.001),tPSA (P ＜ 0.00l) and biopsy Gleason score levels (P =0.006) were higher in patients with extraprostatic extension than that in patients with organ-confined disease,and prostate volume was lower(P =0.009).MRI PSAD showed the largest area under ROC curve (AUC) among those parameter(AUC =0.852,P ＜ 0.001),and tPSA was the second (AUC =0.764).Multivariate logistic regression analyses showed that MRI PSAD was an independent predictor of extraprostatic extension.Conclusions MRI PSAD was better than tPSA in predicting pathological stage of extraprostatic extension.The value of PSAD should not be ignored in the prediction of pathological stage.

Inhibition of autophagy leads to increased apoptosis in LNCaP cells under androgen deprivation conditions / 中华泌尿外科杂志

Objective To investigate the change of apoptosis in LNCaP cells after inhibition of autophagic process under androgen removal conditions. Methods The autophagic level was deter-mined by using confocal microscopy and RT-PCR. The DAPI staining was used to indicate the apopto-sis of LNCaP cells after inhibition of autophagic by 3-MA. Also, Z-VAD-FMK was used to extend the apoptosis results. Results ①Androgen deprivation led to increased autophagy in LNCaP cells. LN-CaP cells cultured in complete medium(CM) presented low autophagic process with 1.9 scores. After 24 hours, the punetate GFP-LC3 structures were accumulated in the cells cultured in serum-free medi-um (SF)(2.64 scores). In contrast, the number of punctate GFP-LC3 remained at a very low level (1.85 scores), when cells were incubated with DHT in SFA(serum-free medium+DHT). Statistical analysis showed the significant difference between SF and SFA (P<0.01). Semiquantitative RT-PCR was employed to examine the mRNA expression of LC3. Indeed, cells grown in the medium without serum had a higher LC3 mRNA expression with the highest at 12 hour time point as compared with the cells grown in CM. DHT treatment reduced the level of LC3 mRNA. ②Blockage of autophagy by 3-MA increased the apoptosis of LNCaP cells. LNCaP cells in SF and SFA just presented a basal level of apoptosis, which is (3.19±1.09)% and (3.01±0.33)% , respectively. Under androgen-free con-ditions, inhibition of autophagy by 3-MA could increase apoptosis significantly(10. 90±2.91%). While Z-VAD-FMK, a pan Caspase inhibitor, was able to suppress this apoptotic process to the level of (1.16±0.52)%, which was statistically significant(P<0.01). Conclusions Androgen removal can lead to the increase of autophagy in LNCaP cells. Moreover, inhibition of autophagy promotes the occurrence of apoptosis.

Empirical study for sensitized dendritic cells in the treatment of bladder tumor / 肿瘤研究与临床

Objective To study the effects of sensitized dendritic cells in the treatment of bladder tumor and further discuss the mechanism of this immunotherapy. Methods 44 female F344 rats, which irrigated N-methyl-N-nitrosourea into bladders every other week for a total of five doses, were induced to bladder tumor. They were treated subcutaneously with either PBS, unsensitized DC, freeze thawing supernatant of tumor cells, or sensitized DC respectively every week for a total of four times. In the fifteenth week, their bladders were weighted and harvested for observation by naked eye and microscope, their blood was harvested for examination CTL by FCM. Results The weight of bladders in sensitized DC group was lower than those in PBS group, unsensitized DC group and freeze thawing supernatant of bladder tumor cells group (P<0.05). The stages of bladder tumor in sensitized DC group were statistically descended compared with those in PBS group (P <0.05). The CD+3 T cells in sensitized DC group was lower than those in PBS group, unsensitized DC group and freeze thawing supernatant of bladder tumor cells group (P <0.05). The CD+3 CD+8 CD+28 T cells in sensitized DC group was higher than those in PBS group, unsensitized DC group and freeze thawing supematant of bladder tumor cells group(P <0.001). Conclusion Sensitized DC injecting subcutaneously can reduce the stages of F344 rats' bladder tumor, Unsensitized DC injecting subcutaneously has not effect in the treatment of bladder tumor;, while the effect of freeze thawing supematant of tumor cells injecting subcutaneously is not well. The mechanism of sensitized DC in the treatment of blader tumor is that DC plays an immunol killing role by presenting antigen, stimulating CTL.